🧪 TrialInsufficient
Registered Phase 4 interventional trial (not yet recruiting). Prediabetes affects millions of adults worldwide and carries a high risk of progression to type 2 diabetes. Mazdutide is a once-weekly injectable drug that activates both GLP-1 and glucagon receptors, lowering blood sugar and body weight simultaneously. This study (DREAM-PRE) tests whether mazdutide can help adults with prediabetes return to normal blood sugar levels. Approximately 150 adults aged 18-75 years with prediabetes and BMI ≥22 kg/m² will be randomly assigned in equal numbers to one of three groups: mazdutide 4 mg once wee
ClinicalTrials.gov · Jun 2026View trial ↗ Moderate · humanPreprint
This Bayesian network meta-analysis systematically evaluated the dose-dependent efficacy and safety of mazdutide — a dual GLP-1 receptor and glucagon receptor agonist — in adults with obesity or overweight, with or without type 2 diabetes. Researchers searched five major databases through January 2026 and included nine randomized controlled trials comprising 2,292 participants. The study found that, compared with placebo, multiple mazdutide doses were associated with statistically significant improvements across a broad range of cardiometabolic outcomes, including body weight, waist circumference, BMI, HbA1c, fasting plasma glucose, blood pressure, LDL cholesterol, and liver enzymes (ALT). Subgroup analyses suggested that weight loss effects were more pronounced in non-diabetic individuals, while glycemic benefits were greater in those with type 2 diabetes. Gastrointestinal adverse events were notably more frequent with mazdutide relative to placebo, though serious adverse events were not significantly elevated. Key limitations include the relatively small number of included trials (n=9) and total participants, the indirect comparisons inherent to network meta-analysis methodology, potential heterogeneity across trial populations, and the preprint status of this work, meaning it has not yet undergone formal peer review.
Unknown journal · Jun 2026DOI ↗ Strong · human
The GLORY-2 trial was a double-blind, placebo-controlled, phase 3 randomized clinical trial evaluating the efficacy and safety of mazdutide — a once-weekly subcutaneous glucagon and GLP-1 receptor dual agonist — for weight reduction in Chinese adults with obesity (BMI ≥30). Conducted across 27 hospitals in China from December 2023 to November 2025, the trial enrolled 461 participants (64% female; mean age ~34 years; mean BMI ~34.3), including 16.1% with type 2 diabetes. Participants were randomized 2:1 to receive 9 mg mazdutide or placebo weekly for 60 weeks alongside lifestyle interventions. The co-primary outcomes were percentage change in body weight and proportion achieving ≥5% weight loss at week 60. The mazdutide group achieved a mean body weight reduction of approximately 16.65% from baseline, compared with 1.50% in the placebo group — a statistically significant between-group difference of approximately 15.15%. Gastrointestinal adverse reactions were more common in the mazdutide group than in the placebo group. Key limitations include the single-ethnicity (Chinese) population, limiting generalizability, and a relatively young mean participant age. The trial was industry-relevant and registered on ClinicalTrials.gov (NCT06164873).
Review
This review synthesizes evidence from randomized controlled trials and high-quality meta-analyses on approved and investigational obesity medications, examining their effects beyond weight loss alone. Medications reviewed include phentermine-topiramate, naltrexone-bupropion, GLP-1 receptor agonists (liraglutide, semaglutide), and newer multiagonist agents (tirzepatide, survodutide, mazdutide, retatrutide, cagrilintide-semaglutide, and amycretin). The authors evaluated impacts across a broad range of obesity-related comorbidities, including type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, chronic kidney disease, heart failure, cardiovascular disease, obstructive sleep apnea, polycystic ovary syndrome, osteoarthritis, muscle mass, depression, quality of life, food cravings, binge-eating disorders, substance use disorders, and neurodegenerative diseases. The review concludes that GLP-1-based and multiagonist therapies demonstrate beneficial effects across these conditions. Notably, the authors report that while many benefits appear to be mediated through weight reduction, accumulating evidence suggests weight loss-independent mechanisms, particularly for GLP-1 receptor agonist-based therapies. Key limitations include its reliance on synthesized rather than primary data and variability in evidence quality across the individual conditions reviewed.
The lancet. Diabetes & endocrinology · May 2026DOI ↗ Review
This review paper systematically examines the patent landscape and therapeutic development trajectory of mazdutide, a dual GLP-1 receptor (GLP-1R) and glucagon receptor (GCGR) agonist being investigated for obesity and type 2 diabetes. Using the Patentscope database, the authors analyzed 12 patent families filed between 2015 and 2025, covering composition-of-matter, process chemistry, formulation technologies, dosing regimens, and therapeutic applications. The review traces innovation from early peptide design work by Eli Lilly to formulation, clinical, and indication-expansion strategies later pursued by Innovent Biologics, including applications in obesity, type 2 diabetes, hyperuricemia, and adolescent obesity. The authors argue that mazdutide's development illustrates a "layered" intellectual property strategy — integrating molecular design, manufacturability, formulation stability, and clinical-use claims — as a model for securing durable market exclusivity for next-generation peptide therapeutics. Limitations include that this is a review and patent analysis rather than a clinical study, so it does not directly evaluate patient outcomes, safety, or comparative efficacy. The paper provides strategic and historical context for mazdutide's development rather than original experimental data.
Expert opinion on therapeutic patents · Mar 2026DOI ↗ Moderate · human
This phase 2 randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of mazdutide 9 mg — a once-weekly dual glucagon and glucagon-like peptide-1 (GLP-1) receptor agonist — in Chinese adults with obesity (BMI ≥30 kg/m²) without diabetes over 24 weeks. Eighty participants were randomized 3:1 to receive mazdutide 9 mg (n=60) or placebo (n=20). The primary endpoint was percentage change in body weight from baseline to week 24. The study found that participants receiving mazdutide 9 mg experienced a mean body weight reduction of approximately 12.78%, compared to a gain of 1.80% in the placebo group, representing a treatment difference of approximately −14.58% (95% CI: −18.00 to −11.16). The authors concluded that mazdutide 9 mg was safe and produced substantial weight reductions in this population. Key limitations include the relatively small sample size, the short 24-week duration, the single-country (China) population limiting generalizability, the phase 2 (exploratory) design, and industry sponsorship by Innovent Biologics. The findings are described as supportive of further clinical development.
Med (New York, N.Y.) · Mar 2026DOI ↗ Review
This narrative review examines the rapidly evolving landscape of obesity pharmacotherapy, moving beyond currently approved injectable GLP-1 receptor agonists (GLP-1RAs). The authors contextualize the global obesity burden—affecting over 2 billion adults—and acknowledge the transformative but limited success of existing GLP-1-based therapies, citing weight loss plateaus, high inter-individual variability, and weight regain upon discontinuation as key unresolved challenges. The review synthesizes emerging drug classes including: oral GLP-1 agonists (e.g., orforglipron) aimed at improving global accessibility; multi-receptor agonists such as triple GLP-1/GIP/glucagon agonists (e.g., retatrutide, reportedly achieving 20–24% weight reduction) and dual GLP-1/glucagon agonists (e.g., survodutide, mazdutide) with potential benefits in metabolic-associated steatotic liver disease; novel dosing strategies via GLP-1/GIP combination agents (e.g., maridebart cafraglutide); amylin pathway agents (e.g., cagrilintide, amycretin); lean-mass-preserving agents (e.g., bimagrumab); and precision approaches for monogenic obesity (e.g., setmelanotide). The authors call for phenotype-stratified trials, long-term safety data, pediatric research, and equitable implementation. As a review, it does not present original trial data and is inherently subject to selection and interpretation bias.
Metabolism open · Mar 2026DOI ↗ Moderate · human
This meta-analysis pooled data from five randomised controlled trials to evaluate the efficacy and safety of mazdutide — a dual GLP-1 and glucagon receptor agonist — for weight management in non-diabetic adults with overweight or obesity. Searches were conducted across Cochrane Library, PubMed, Google Scholar, and ClinicalTrials.gov, and analyses were performed using random-effects models in RevMan 5.4. The pooled results reported by the study authors indicate that mazdutide was associated with significant reductions in percentage body weight (mean difference –12.42%), absolute body weight (–9.76 kg), and waist circumference (–7.98 cm) compared with control conditions. Secondary cardiometabolic outcomes — including systolic blood pressure (–7.68 mmHg), total cholesterol (–0.57 mmol/L), and LDL cholesterol (–0.37 mmol/L) — also showed reductions. Adverse events were slightly more frequent in the mazdutide groups (RR = 1.12), described as mild to moderate. A dose-wise meta-regression suggested a significant dose-dependent relationship. The authors acknowledge that findings are constrained by the small number of included trials (n = 5), which limits the robustness and generalisability of conclusions.
Diabetes, obesity & metabolism · Mar 2026DOI ↗ Moderate · human
This network meta-analysis systematically evaluated the comparative efficacy and safety of four investigational glucagon receptor agonist (GRA)-based agents — retatrutide, cotadutide, mazdutide, and survodutide — in adults with type 2 diabetes, overweight, or obesity. Researchers searched PubMed, Cochrane, Embase, and Scopus, ultimately including 14 randomised controlled trials analyzed using frequentist network meta-analysis with random-effects models. Key outcomes included absolute and percent body weight change, HbA1c reduction, adverse events, and treatment discontinuation due to adverse events. The study found that retatrutide produced the greatest absolute weight reduction versus placebo (MD −13.44 kg), followed by survodutide (MD −10.74 kg) and mazdutide (MD −6.47 kg); cotadutide's effect did not reach statistical significance. Retatrutide also showed the largest HbA1c reduction, though only its effect was statistically significant among the agents. Regarding tolerability, mazdutide demonstrated the most favorable safety profile, while retatrutide and cotadutide were associated with comparatively lower tolerability. The authors acknowledge limitations inherent to network meta-analysis, including reliance on early- and mid-phase trial data and the absence of direct head-to-head comparisons between agents.
Endocrinology, diabetes & metabolism · Mar 2026DOI ↗ Review
This review examines the landscape of next-generation glucagon-like peptide-1 (GLP-1)-based therapeutics in clinical development for type 2 diabetes and obesity, building on the established success of semaglutide and tirzepatide. The authors survey a broad range of investigational agents that target multiple gastro-entero-pancreatic hormone receptors simultaneously — including GIP, glucagon, amylin, and peptide YY receptors — to produce synergistic effects on energy intake, storage, and expenditure. Specific agents discussed include maridebart cafraglutide (GLP-1 agonism/GIP antagonism), survodutide and mazdutide (GLP-1/glucagon coagonists), cagrilintide combined with semaglutide (CagriSema), amycretin (amylin/GLP-1 dual agent), and retatrutide (GIP/GLP-1/glucagon triple agonist). The review also highlights the emergence of oral small-molecule GLP-1 receptor agonists such as danuglipron and orforglipron, which resist enzymatic degradation and may improve patient convenience. The paper does not present original clinical trial data; it synthesizes existing preclinical and clinical development evidence. As a narrative review, it does not meta-analytically pool outcomes, and the included agents are largely at Phase 1–3 stages, meaning long-term efficacy and safety data remain limited.
Endocrine reviews · Mar 2026DOI ↗ Preclinical
This study investigated whether mazdutide, a dual GLP-1/glucagon receptor agonist previously studied for weight and metabolic management, could reduce early-stage metabolic dysfunction-associated steatotic liver disease (MASLD). Researchers used two model systems: mice fed a high-fat diet for 12 weeks (then treated with subcutaneous mazdutide for 4 weeks) and hepatocytes exposed to free fatty acids in cell culture (then co-treated with mazdutide or an ER stress inhibitor). The study measured blood and liver lipid profiles, liver injury markers, inflammatory cytokines, oxidative stress indicators, and liver histology, as well as protein expression linked to endoplasmic reticulum (ER) stress, inflammation, and lipid metabolism. The authors report that mazdutide treatment was associated with improved lipid metabolism, reduced hepatic steatosis, lower liver injury markers, and decreased inflammation and oxidative stress in both the animal and cell models. Mechanistically, the authors propose that mazdutide acts at least partly by dampening ER stress pathways. Key limitations include the exclusive use of preclinical models (no human subjects), a single mouse strain/diet protocol, and the early-stage disease focus, meaning translation to human MASLD remains unestablished.
Pharmaceuticals (Basel, Switzerland) · Feb 2026DOI ↗ Strong · human
This systematic review and meta-analysis pooled data from 10 randomized controlled trials (3,236 participants) to evaluate the efficacy and safety of incretin-based dual and triple receptor agonists — specifically tirzepatide, retatrutide, and mazdutide — in overweight or obese adults. The authors searched PubMed, the Cochrane Library, and Google Scholar through June 2025 and applied a random-effects model to pool outcomes. The study found that these agents were associated with statistically significant reductions in body weight (mean difference: −11.47 kg), waist circumference (−9.40 cm), glycated hemoglobin (−0.96%), and fasting plasma glucose (−26.89 mg/dL) compared to placebo. On the safety side, treatment was associated with a higher risk of any adverse event (RR 1.13), gastrointestinal adverse events (nausea, vomiting, diarrhea, constipation), treatment discontinuation due to adverse events (RR 1.96), and hypoglycemic episodes (RR 3.08). No significant difference in serious adverse events was observed. Limitations include the relatively small number of pooled trials, heterogeneity inherent across different agents and doses, and the restriction to placebo-controlled comparisons, which limits conclusions about comparative effectiveness between agents.
Cardiology in review · Feb 2026DOI ↗ Review
This Chinese clinical comprehensive evaluation systematically compared five long-acting GLP-1 receptor agonists (dulaglutide, semaglutide, polyethylene glycol loxenatide, tirzepatide, and mazdutide) for the management of type 2 diabetes within China's healthcare context. The researchers constructed a quantitative, six-dimensional scoring framework—covering efficacy, safety, economy, innovation, suitability, and accessibility—with indicator weights derived through a Delphi expert consultation process. Evidence sources included drug labels, systematic literature reviews, and real-world data. Semaglutide scored highest (76.6/100) followed by dulaglutide (72.6), polyethylene glycol loxenatide (64.8), tirzepatide (62.9), and mazdutide (55.1). Semaglutide and dulaglutide were classified as "Strong Recommendations," largely due to superior cardio-renal outcome evidence. Tirzepatide and polyethylene glycol loxenatide received "Conditional Recommendations," while mazdutide was "Not Recommended" owing to insufficient evidence, lack of national reimbursement listing, and high cost. Key limitations include the inherent subjectivity of the Delphi weighting process, the China-specific formulary and reimbursement context limiting global generalizability, and the composite nature of the scoring system potentially obscuring individual domain differences.
Diabetes, metabolic syndrome and obesity : targets and therapy · Feb 2026DOI ↗ Animal onlyPreprint
This preclinical study investigated whether mazdutide — a dual GLP-1/glucagon receptor agonist that has shown clinical promise for weight management and metabolic disorders — could alleviate non-alcoholic fatty liver disease (NAFLD) and explored its potential mechanism of action. Researchers induced NAFLD in mice via a 12-week high-fat diet, then treated animals with subcutaneous mazdutide for four weeks. Complementary in vitro experiments exposed hepatocytes to free fatty acids to model hepatic steatosis, followed by mazdutide co-treatment. The study measured serum and liver lipid profiles, liver injury markers, inflammatory cytokines, oxidative stress indicators, and key protein expression via Western blot and immunohistochemistry. Results indicated that mazdutide treatment was associated with reduced hepatic fat accumulation, lower liver injury markers, attenuated inflammation, and decreased oxidative stress in both models. Mechanistically, the authors attributed these effects to modulation of the PERK–eIF2α–ATF4–CHOP endoplasmic reticulum (ER) stress pathway, suppression of NF-κB-driven inflammation, and downregulation of lipogenic regulators (SREBP-1, C/EBPβ, PPARγ). Key limitations include the exclusive use of animal and cell-based models, lack of human data, and preprint status meaning findings have not yet undergone formal peer review.
Unknown journal · Jan 2026DOI ↗ Moderate · human
This Phase 3 randomized controlled trial evaluated mazdutide, a dual glucagon receptor (GCGR) and GLP-1 receptor (GLP-1R) agonist, as monotherapy versus placebo in 320 Chinese adults with type 2 diabetes (T2D) inadequately controlled by diet and exercise. Participants had a mean HbA1c of 8.24% and BMI of 28.2 kg/m². They were randomized 1:1:1 to weekly subcutaneous injections of mazdutide (4 mg or 6 mg) or placebo for 24 weeks, followed by a 24-week mazdutide extension phase. At week 24, the study found that both mazdutide doses significantly reduced HbA1c versus placebo (−1.57% and −2.15% for 4 mg and 6 mg, respectively, vs. −0.14% for placebo). Both doses also produced significantly greater body weight reductions and improved rates of composite endpoints (HbA1c <7.0% with ≥5% weight loss) compared to placebo. The most common adverse events—diarrhea, decreased appetite, and nausea—were consistent with the GLP-1R agonist class. Limitations include the single-ethnicity population (Chinese adults), the relatively short 24-week primary endpoint period, and the lack of an active comparator arm, which limits generalizability and comparative effectiveness conclusions.
Moderate · human
This Phase III randomized controlled trial evaluated mazdutide, a novel once-weekly dual glucagon and GLP-1 receptor agonist, compared to dulaglutide in 731 Chinese adults with type 2 diabetes (T2D) on background oral anti-diabetic therapy. Participants were randomized 1:1:1 to one of two mazdutide doses or dulaglutide (1.5 mg) for 28 weeks. The study found that both mazdutide doses demonstrated non-inferiority and superiority to dulaglutide in reducing HbA1c from baseline, with least-squares mean treatment differences of -0.24% and -0.30% for the lower and higher doses, respectively. Mazdutide also produced significantly greater reductions in body weight than dulaglutide, with differences of -3.78% and -5.76% for the two doses. The safety profile was generally acceptable, though gastrointestinal adverse events occurred more frequently with mazdutide than dulaglutide. Limitations include the relatively short 28-week duration, restriction to a Chinese population, and the lack of a placebo arm, which may limit generalizability of findings.
Insufficient
The DREAMS-3 trial is a randomized, open-label Phase 3 study designed to compare the efficacy and safety of mazdutide (a glucagon receptor/GLP-1 receptor co-agonist) versus semaglutide (a GLP-1 receptor agonist) in Chinese adults with type 2 diabetes (T2D) and obesity. This publication reports the trial's rationale, design, and baseline characteristics rather than outcome results, as the study is ongoing with an expected completion date in early 2026. A total of 349 participants (mean age 42.4 years; 44.7% male) were randomized 1:1 to either treatment arm for a 32-week active-controlled period followed by a 24-week extension. At baseline, participants had a mean HbA1c of 8.0%, body weight of 90.5 kg, and BMI of 33.0 kg/m². The mean T2D duration was 1.8 years, and approximately 39.5% were on metformin. The primary endpoint is the proportion of participants achieving HbA1c targets. Notably, comorbidities such as metabolic-associated fatty liver disease and gout/hyperuricemia showed strong associations with BMI. As a design and baseline data paper, no efficacy or safety outcomes are yet available, limiting current evidence value.
Contemporary clinical trials · Nov 2025DOI ↗ Moderate · humanPreprint
This meta-analysis pooled data from four randomized controlled trials (n = 918) to evaluate the efficacy of mazdutide — a dual GLP-1 and glucagon receptor agonist — in nondiabetic adults with overweight or obesity. Researchers searched PubMed, Scopus, and Web of Science and applied a random-effects model to analyze primary outcomes including body weight, BMI, and waist circumference, along with secondary cardiometabolic markers. The pooled analysis found that, compared with placebo, mazdutide was associated with statistically significant reductions in body weight (mean difference: −7.72 kg), BMI (−2.84 units), waist circumference (−5.76 cm), HbA1c (−0.30%), LDL cholesterol (−10.59 mg/dL), total cholesterol (−18.61 mg/dL), and triglycerides (−49.87 mg/dL). The authors concluded that mazdutide shows promise as a pharmacotherapy option for this population. Key limitations include the small number of included trials (n = 4), the relatively modest total sample size, the lack of long-term follow-up data, and the preprint status of this analysis, meaning it has not yet undergone formal peer review. Findings should therefore be interpreted with caution pending publication.
Unknown journal · Oct 2025DOI ↗ Review
This article is a regulatory milestone review summarizing the development history of mazdutide (Xinermei®), a dual glucagon receptor (GcgR) and glucagon-like peptide-1 receptor (GLP-1R) agonist co-developed by Eli Lilly and Innovent Biologics. The review traces the compound's path to its first regulatory approval in China in June 2025 for long-term body weight management in adults with obesity (BMI ≥28 kg/m²) or overweight with comorbidities (BMI ≥24 kg/m²), alongside diet and physical activity. A subsequent Chinese approval for glycemic control in type 2 diabetes followed in September 2025. The article also notes ongoing clinical investigations into metabolic dysfunction-associated fatty liver disease, obstructive sleep apnea, and alcohol use disorder. As a "First Approval" narrative review, it consolidates developmental milestones rather than presenting original trial data. It does not independently report clinical outcomes, efficacy effect sizes, or safety data from primary studies, limiting the ability to assess the strength of underlying evidence directly from this article alone.
Limited · human
This case report describes the use of Mazdutide, a dual glucagon-like peptide-1/glucagon receptor (GLP-1/GCGR) agonist, in a 15-year-old male presenting with obesity (BMI 30.64 kg/m²), type 2 diabetes (HbA1c 9.60%), and hyperuricemia (serum uric acid 511 µmol/L). The patient received a dose-escalation regimen of subcutaneous once-weekly Mazdutide alongside metformin and insulin over 36 weeks. The authors report substantial improvements across multiple metabolic parameters: body weight decreased by 16.8 kg (18.89% BMI reduction), HbA1c fell by 21.88%, and serum uric acid dropped by 37.00%. Lipid outcomes also improved, with triglycerides declining 69.02%, total cholesterol 13.65%, and LDL cholesterol 17.27%. Hepatic steatosis, confirmed by ultrasound, resolved by week 14. No hypoglycemic episodes or other adverse events were reported, and benefits were described as sustained after treatment ended. Key limitations include the single-patient design, the absence of a control condition, and the concurrent use of metformin and insulin, making it impossible to attribute outcomes specifically to Mazdutide. These preliminary observations may inform future controlled studies in adolescent populations.
Frontiers in endocrinology · Sep 2025DOI ↗